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リモノ類および三環系ジテルペノイドのメラニン生成抑制活性
Melanogenesis-inhibitory activities of limonoids and tricyclic diterpenoids from Azadirachta indica.
PMID: 32450387 DOI: 10.1016/j.bioorg.2020.103941.
抄録
Azadirachta indicaの根と樹皮の化学成分を調べた結果、6種類の三環系ジテルペノイドと4種類のリモノを分離した。また、NMR分光法、質量分析法、文献との比較を行い、その構造を明らかにした。さらに、単離された化合物のメラニン生成抑制活性を評価した。その結果、化合物１〜３及び１０は、細胞に対する毒性がないか、ほとんどない（細胞生存率86.5〜105.1％）、優れたメラニン生成抑制活性を示した。ウェスタンブロット分析の結果、α-MSH刺激を受けたB16メラノーマ細胞において、化合物1及び3は、少なくとも一部でMITFの発現を阻害し、次いでチロシナーゼ、TRP-1及びTRP-2の発現を低下させることにより、メラニン生成抑制活性を示した。化合物1および3はチロシナーゼ阻害活性を示した（IC値はそれぞれ44.86μMおよび69.85μM）。化合物1と化合物3はチロシナーゼ阻害活性を示した（IC値44.86×3BC, M, 69.85×3BC, M）。
The chemical constituents of the roots and bark of Azadirachta indica were investigated, leading to the isolation of six tricyclic diterpenoids and four limonoids including a new compound, azadirachtin J (4). The structures were elucidated on the basis of NMR spectroscopic techniques, mass spectrometry as well as comparison with the literature. Furthermore, melanogenesis-inhibitory activities of the isolated compounds were evaluated. As a result, compounds 1-3 and 10 exhibited superior inhibitory activities against melanogenesis with no, or almost no, toxicity to the cells (86.5-105.1% cell viability). Western blot analysis showed that compounds 1 and 3 exhibited melanogenesis inhibitory activities in α-MSH-stimulated B16 melanoma cells due to, at least in part, inhibition of the expression of MITF, followed by a decrease in the expression of tyrosinase, TRP-1, and TRP-2. Compounds 1 and 3 exhibited tyrosinase inhibitory activities (IC values of 44.86 μM and 69.85 μM respectively). Docking results confirm that the active inhibitors strongly interact with tyrosinase residues.
Copyright © 2020 Elsevier Inc. All rights reserved.